The long term goal of this research is to understand the immunochemical basis of human immune response, using inhaled pollen allergens as a model. We will isolate three groups of allergenic proteins in ultra-pure state, toward which responsiveness is associated with HLA-DR2/Dw2, DR5, or DR3/Dw3. Studies of Ia determinants, recognized by different human HLA-D specificities, and of B-cell determinants, recognized by different human IgE and IgG antibodies, will be carried out. In particular, we will address the question regarding how immune responsiveness toward multiple non-crossreactive antigens can be associated with the same HLA-DR specificity. Immunochemical studies will be carried out using three groups of pollen allergens: a) the homologous group of Amb V (Ra5) allergens from three or four species of Ambrosiinae (ragweed sub-tribe), toward which immune responsiveness is associated with HLA-DR2/Dw2; b) the homologous group of Amb VI (Ra6) allergens from at least two species of Ambrosiinae, toward which responsiveness is associated with HLA-DR5 for the Amb a VI (short ragweed Ra6) prototype; c) the related Lo1 p I, II and III (Rye I, II and III) allergens from Lolium perenne pollen, toward which responsiveness is associated with HLA-DR3/Dw3. DNA Restriction Fragment Length Polymorphisms will be studied using a DR2B ta probe among several different Amb V-responder/non-responder phenotypes in order to investigate the heterogeneity of HLA-DR2 within the various subjects. We will also continue collaborative studies on the role of auto-anti-idiotypes in regulating the levels of specific IgG and IgE antibodies to Lo1 p I in patients receiving grass immunotherapy. A unique asset will be the availability of two well-characterized populations: ca. 350 local clinic patients who have been extensively studied clinically and immunologically as a result of their participation in various studies of allergen immunotherapy at the Good Samaritan Hospital and ca. 500 subjects from an epidemiologic-genetic study of human immune response to allergens.